Metabomomics-based Efficacy Principle Of Shen Fu Decoction Treatment Of Chronic Heart Failure

Objective:Ultra-performance liquid chromatography/time-of-flight mass spectrometry(UPLC/Q-TOF MS)was used to this study SD rats that established model of heart failure,investigating the trend of endogenous small molecule metabolites in rats with chornic heart failure before and after,analyse and clarify potential biomarkers of metabolic mechanisms;Rapid resolution liquid chromatography/tandem mass spectrometry(RRLC-MS/MS)was used in rat urine and heart tissue derived small molecules that absolute quantitative analysis of a variety of amino acids.Methods:Through coronary artery ligation model to establish heart failure of rats,using ACQUITY UPLC 1.8?m type of reversed-phase column,urine and serum of rats in each group were used in conjunction with liquid chromatography detection by standard library search and comparison method to extract and identify relevant biomarkers of heart failure,and to do multivariate statistical analysis to identify potential biomarkers.Use BEH Amide column,the simultaneous determination of nine kinds or ten kinds of urine and heart failure associated with the amino acids within 10min,acetonitrile and 0.1%aqueous formic acid-10mM ammonium formate gradient elution was 0.3mL/min,ion source ESI,positive ion mode scanning,scanning mode is multiple reaction monitoring(MRM).Results:The model of rat with coronary artery ligation metabolic fingerprint with the normal group and sham operation group rats were significantly different by comparing the urine and serum of potential biomarkers,including 16 species of rat urine potential biomarkers,serum has 13 kinds of potential biomarkers matter;compared with normal control group,the rats in the model group increased urine are:arginine?valine?tyrosine?glutamine?azelaic acid?tryptophan?taurine?palmitic acid?stearic acid?citric acid?creatinine?phenylalanine;reduction are:methionine?arachidonic acid and fructose,compared with the normal control group and model group of serum alanine?isoleucine?methionine?tryptophan?valine?arachidonic acid and hippuric acid levels were significantly increased,taurine?histidine?citric acid?glutamine?glutamic acid and arginine levels were significantly reduced,and associated with the discovery of potential biomarkers of heart failure there are common characteristics of both physical and biochemical analysis of metabolic pathways involved in heart failure prompted glucose metabolism,energy metabolism,lipid metabolism and amino acid metabolism,giving Shenfu Decoction these metabolites are small molecules call back,indicating Shenfu Decoction act on these small molecules metabolism.Established simultaneous detection of multiple amino acids in rat urine and heart tissue.This quantitative analysis method was rapid,sensitive and reliable,each amino acid in the detection range of the standard curves showed good linearity(r>0.99),the limits of detection and quantitation were at the Pg level.The intra-and inter-day precision of RSD were less than 15%.Conclusion:Metabolomics can detect a variety of metabolic organic circulation pathway state,and is an effective tool of evaluation of metabolic changes in rats with chronic heart failure model,explore Shenfu Decoction conducted a comprehensive assessment of efficacy at the molecular level foundation.